8pba

Cryo-EM structure of Caenorhabditis elegans DPF-3 (apo)

spinqualitylabelsall models 8pba, resolution 2.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8pba is a 2 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.64Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q965K3_CAEEL Publication Abstract from PubMed Substrate specificity determines protease functions in physiology and in clinical and biotechnological applications, yet quantitative cleavage information is often unavailable, biased, or limited to a small number of events. Here, we develop qPISA (quantitative Protease specificity Inference from Substrate Analysis) to study Dipeptidyl Peptidase Four (DPP4), a key regulator of blood glucose levels. We use mass spectrometry to quantify >40,000 peptides from a complex, commercially available peptide mixture. By analyzing changes in substrate levels quantitatively instead of focusing on qualitative product identification through a binary classifier, we can reveal cooperative interactions within DPP4's active pocket and derive a sequence motif that predicts activity quantitatively. qPISA distinguishes DPP4 from the related C. elegans DPF-3 (a DPP8/9-orthologue), and we relate the differences to the structural features of the two enzymes. We demonstrate that qPISA can direct protein engineering efforts like the stabilization of GLP-1, a key DPP4 substrate used in the treatment of diabetes and obesity. Thus, qPISA offers a versatile approach for profiling protease and especially exopeptidase specificity, facilitating insight into enzyme mechanisms and biotechnological and clinical applications. Deep quantification of substrate turnover defines protease subsite cooperativity.,Gudipati RK, Gaidatzis D, Seebacher J, Muehlhaeusser S, Kempf G, Cavadini S, Hess D, Soneson C, Grosshans H Mol Syst Biol. 2024 Dec;20(12):1303-1328. doi: 10.1038/s44320-024-00071-4. Epub , 2024 Oct 28. PMID:39468329 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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